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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT01121575
Registration number
NCT01121575
Ethics application status
Date submitted
10/05/2010
Date registered
12/05/2010
Date last updated
28/10/2015
Titles & IDs
Public title
A Study Of Combined C- MET Inhibitor And PAN-HER Inhibitor (PF-02341066 And PF-00299804) In Patients With Non- Small Cell Lung Cancer
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Scientific title
A Phase 1, Open-label, Dose Escalation Study To Evaluate Safety, Pharmacokinetics And Pharmacodynamics Of Combined Oral C-met/Alk Inhibitor (Pf-02341066) And Pan-her Inhibitor (Pf-00299804) In Patients With Advanced Non-small Cell Lung Cancer
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Secondary ID [1]
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A8081006
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Non Small Cell Lung Cancer
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Condition category
Condition code
Cancer
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Lung - Mesothelioma
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Cancer
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Lung - Non small cell
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Cancer
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Lung - Small cell
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - PF-02341066
Treatment: Drugs - PF-00299804
Treatment: Drugs - PF-02341066
Treatment: Drugs - PF-00299804
Experimental: Arm 1 - PF-02341066 AND PF-00299804: Patients will be treated with combined cMET inhibitor (PF-02341066) and panHER inhibitor (PF-00299804).
Experimental: Arm 2 - PF-00299804 FOLLOWED BY COMBINED PF-02341066 AND PF-00299804: Patients will be treated with single agent panHER inhibitor (PF-00299804) until disease progression and then with the maximum tolerated combined dose of cMET inhibitor (PF-02341066) and panHER inhibitor (PF-00299804).
Treatment: Drugs: PF-02341066
Arm 1: The starting dose will be 200 mg by mouth, twice a day of PF 02341066 in tablet form The dose of each drug in the combination \[PF-02341066 and PF-00299804\] will be escalated or de-escalated until the maximum tolerated combined dose is reached. Patients will then be treated with the maximum tolerated combined dose.
Treatment: Drugs: PF-00299804
Arm 1: The starting dose will be 30 mg by mouth once a day of PF-0029804 in tablet form. The dose of each drug in the combination \[PF-02341066 and PF-00299804\] will be escalated or de-escalated until the maximum tolerated combined dose is reached. Patients will then be treated with the maximum tolerated combined dose.
Treatment: Drugs: PF-02341066
Arm 2: With progressive disease the maximum tolerated combined dose of PF-02341066 (given by mouth twice a day in tablet form) and PF-00299804 (given by mouth once a day in tablet form).
Treatment: Drugs: PF-00299804
Arm 2: The dose of 45 mg by mouth once a day of PF-00299804 in tablet form until progressive disease and then the maximum tolerated combined dose of PF-02341066 (given by mouth twice a day in tablet form) and PF-00299804 (given by mouth once a day in tablet form).
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Overview of Treatment-emergent All Causalities Adverse Events (AEs) in Escalation Phase
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Assessment method [1]
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AE was any untoward medical occurrence with study drug/ device in a trial participant. Serious adverse event (SAE) was an AE resulting in death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsen in severity after the first dose of study medication. AEs were reported from signing of informed consent until 28 days after the last dose of study medication. SAEs were reported after this time frame if considered to be treatment related. The severity of AEs were graded by the investigator using National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE) v.4.02 and was assessed as Grade 0: no change from normal or reference range; Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening or disabling; Grade 5: death related to AE. However the below table included Grade 3, 4, and 5 AEs.
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Timepoint [1]
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Up to Maximum of treatment duration + 28 days for each participant (could be 295 days)
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Primary outcome [2]
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Overview of Treatment-emergent All Causalities AEs in Expansion Phase
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Assessment method [2]
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AE was any untoward medical occurrence with study drug/ device in a trial participant. SAE was an AE resulting in death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsen in severity after the first dose of study medication. AEs were reported from signing of informed consent until 28 days after the last dose of study medication. SAEs were reported after this time frame if considered to be treatment related. The severity of AEs were graded by the investigator using NCI CTCAE v.4.02 and was assessed as Grade 0: no change from normal or reference range; Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening or disabling; Grade 5: death related to AE. However the below table included Grade 3, 4, and 5 AEs.
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Timepoint [2]
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Up to Maximum of treatment duration + 28 days for each participant (could be 295 days)
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Primary outcome [3]
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Overview of Treatment-emergent, Treatment-related AEs in Escalation Phase
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Assessment method [3]
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An AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. SAE was an AE resulting in death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsen in severity after the first dose of study medication. AEs were reported from signing of informed consent until 28 days after the last dose of study medication. SAEs were reported after this time frame if considered to be treatment related. The severity of AEs were graded by the investigator using NCI CTCAE v.4.02 and was assessed as Grade 0: no change from normal or reference range; Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening or disabling; Grade 5: death related to AE. However the below table included Grade 3, 4, and 5 AEs.
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Timepoint [3]
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Up to Maximum of treatment duration + 28 days for each participant (could be 295 days)
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Primary outcome [4]
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Overview of Treatment-emergent, Treatment-related AEs in Expansion Phase
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Assessment method [4]
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An AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. SAE was an AE resulting in death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsen in severity after the first dose of study medication. AEs were reported from signing of informed consent until 28 days after the last dose of study medication. SAEs were reported after this time frame if considered to be treatment related. The severity of AEs were graded by the investigator using NCI CTCAE v.4.02 and was assessed as Grade 0: no change from normal or reference range; Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening or disabling; Grade 5: death related to AE. However the below table included Grade 3, 4, and 5 AEs.
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Timepoint [4]
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Up to Maximum of treatment duration + 28 days for each participant (could be 295 days)
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Primary outcome [5]
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Number of Participants With Dose Limiting Toxicities (DLTs) in Escalation Phase
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Assessment method [5]
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DLTs were those AEs which occurred in Cycle 1 of treatment in Dose Escalation Phase which may be attributed to study drug \[combined Crizotinib (PF-02341066) plus Dacomitinib (PF-00299804)\] without a clear alternative explanation and despite the use of adequate/maximal medical intervention as dictated by local institutional clinical practices or the judgment of the investigator. The following events were considered DLTs (using CTCAE version 4.02);1. Grade =4 hematologic events. 2. Grade =3 non-hematological events (except Grade 3/4 asymptomatic hypophosphatemia and Grade 3/4 hyperuricemia without signs and symptoms of gout). Nausea, vomiting or diarrhea had to have persisted at Grade 3 or 4 despite maximal medical therapy. Grade 3 hypertension will be considered a DLT only if the event is unmanageable by standard approved pharmacologic agents or if the symptomatic sequelae are identified despite appropriate medical intervention.
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Timepoint [5]
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Cycle 1 (4 weeks)
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Secondary outcome [1]
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Number of Participants With Stable Disease and Stable Disease Duration in Escalation Phase
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Assessment method [1]
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If a participant had not achieved an objective response with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) - 1.1 as determined by the investigators, relative to the response evaluable population, but remained stable for at least 6 weeks after first dose, then the best overall response for such a participant was considered as stable disease.
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Timepoint [1]
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From objective response to date of progression or death due to any cause, whichever occurs first (up to post treatment follow-up as 28-35 days after last dose of study treatment)
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Secondary outcome [2]
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Number of Participants With Stable Disease and Stable Disease Duration in Expansion Phase
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Assessment method [2]
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If a participant had not achieved an objective response with confirmed complete response (CR) or partial response (PR) according to RECIST (1.1) as determined by the investigators, relative to the response evaluable population, but remained stable for at least 6 weeks after first dose, then the best overall response for such a participant was considered as stable disease.
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Timepoint [2]
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From objective response to date of progression or death due to any cause, whichever occurs first (up to post treatment follow-up as 28-35 days after last dose of study treatment)
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Secondary outcome [3]
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Number of Participants With Objective Response Rate (ORR) in Escalation Phase
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Assessment method [3]
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ORR was defined as the percent of participants with CR or PR according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) determined by study physicians, relative to the response evaluable population. Participants were considered non-responders until proven otherwise. Thus, participants who: 1) Did not have CR or PR while on study, or 2) Did not have a post-baseline tumor evaluation, or 3) Received anti-tumor treatment other than the study medication prior to reaching a CR or PR, or 4) Died, in progress, or drop out for any reason prior to reaching a CR or PR, were counted as non-responders in the assessment of ORR. To be assigned a status of PR or CR, changes in tumor measurements in participants with responding tumors were confirmed by repeated tumor assessment that were performed 4 weeks after the criteria for response were first met.
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Timepoint [3]
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From objective response to date of progression or death due to any cause, whichever occurs first (up to post treatment follow-up as 28-35 days after last dose of study treatment)
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Secondary outcome [4]
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Number of Participants With ORR in Expansion Phase
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Assessment method [4]
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ORR was defined as the percent of participants with CR or PR according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) determined by study physicians, relative to the response evaluable population. Participants were considered non-responders until proven otherwise. Thus, participants who: 1) Did not have CR or PR while on study, or 2) Did not have a post-baseline tumor evaluation, or 3) Received anti-tumor treatment other than the study medication prior to reaching a CR or PR, or 4) Died, in progress, or drop out for any reason prior to reaching a CR or PR, were counted as non-responders in the assessment of ORR. To be assigned a status of PR or CR, changes in tumor measurements in participants with responding tumors were confirmed by repeated tumor assessment that were performed 4 weeks after the criteria for response were first met.
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Timepoint [4]
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From objective response to date of progression or death due to any cause, whichever occurs first (up to post treatment follow-up as 28-35 days after last dose of study treatment)
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Secondary outcome [5]
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Duration of Response for the Only Participant Shown Partial Response in Expansion Phase
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Assessment method [5]
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This outcome measure presented the duration of response for one participant in expansion cohort 1 who showed partial response.
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Timepoint [5]
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From objective response to date of progression or death due to any cause, whichever occurs first (up to post treatment follow-up as 28-35 days after last dose of study treatment)
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Secondary outcome [6]
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Progression Free Survival (PFS) in Escalation Phase
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Assessment method [6]
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PFS was defined as the time from the date of the first dose to the date of the first documentation of objective tumor progression according to RECIST 1.1 or death on study due to any cause, whichever occurred first. If tumor progression data included more than 1 date, the first date was used.
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Timepoint [6]
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From randomization to objective tumor progression or death (up to post treatment follow-up as 28-35 days after last dose of study treatment)
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Secondary outcome [7]
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Progression Free Survival (PFS) in Expansion Phase
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Assessment method [7]
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PFS was defined as the time from the date of the first dose to the date of the first documentation of objective tumor progression according to RECIST 1.1 or death on study due to any cause, whichever occurred first. If tumor progression data included more than 1 date, the first date was used.
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Timepoint [7]
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From randomization to objective tumor progression or death (up to post treatment follow-up as 28-35 days after last dose of study treatment)
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Secondary outcome [8]
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Expression Analysis of Tumor Biomarkers (HGF, EGFR, and c-Met ) at Baseline Using Immunohistochemistry (IHC) Method
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Assessment method [8]
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Tumor biomarkers such as HGF, EGFR, and c-Met were analyzed in tumor cells (neoplastic compartment) of tumor specimens from both expansion cohorts 1 and 2 by IHC. The H score was derived by summing the percentages of cells staining at each intensity multiplied by the weighted intensity of staining (0, 1+, 2+, 3+, where 3+ indicates the strongest staining, 2+ indicates medium staining, 1+ indicates weak staining, and 0 indicates no staining). Minimum calculated score of 0 to maximum calculated score of 300, where 0 correspond to no expression and maximum score of 300 indicates the strongest expression. However, the biomarker expression level (higher or lower) was not a predictor of outcome.
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Timepoint [8]
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Baseline
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Secondary outcome [9]
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Expression Analysis of Tumor Biomarkers (EGFR, and c-Met) at Baseline Using Fluorescent in Situ Hybridization (FISH) Method
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Assessment method [9]
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Expression of tumor biomarkers EGFR and cMet at Baseline (using FISH method) are presented in this outcome measure.
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Timepoint [9]
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Baseline
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Secondary outcome [10]
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Number of Participants With c-Met, HER2, EGFR Amplification and ALK Rearrangement at Baseline Using FISH Method
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Assessment method [10]
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Participants showed amplification of c-Met, HER2, and EGFR in the tumor cells and gene rearrangement of ALK are presented in this outcome measure.
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Timepoint [10]
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Baseline
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Secondary outcome [11]
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Plasma Concentration of sMet by Study Visits
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Assessment method [11]
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This outcome measure presented the plasma concentration of sMet at different study visits. s-Met was analyzed using an enzyme-linked immunosorbent assay (ELISA).
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Timepoint [11]
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At screening and Cycle 1 Day 1 (C1D1) (6 hours post dose), and C1D15, C2D1, C2D15 (all predose).
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Secondary outcome [12]
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Number of Participants With EGFR Mutation at Baseline
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Assessment method [12]
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Sample analyses were performed in accordance to Good Laboratory Practice (GLP) guidance and included mutation detection for EGFR gene.
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Timepoint [12]
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Baseline
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Secondary outcome [13]
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Number of Participants With KRAS Mutation (GLY12CYS) at Baseline
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Assessment method [13]
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Sample analyses were performed in accordance to GLP guidance and included mutation detection for KRAS gene.
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Timepoint [13]
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Baseline
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Secondary outcome [14]
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Number of Participants With PIK3CA Mutation at Baseline
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Assessment method [14]
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Sample analyses were performed in accordance to GLP guidance and included mutation detection for PIK3CA gene.
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Timepoint [14]
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Baseline
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Secondary outcome [15]
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Number of Participants With ROS1 Gene Translocation at Baseline
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Assessment method [15]
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Sample analyses were performed in accordance to GLP guidance and included translocation detection (RNA based) for ROS1 gene.
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Timepoint [15]
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Baseline
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Secondary outcome [16]
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Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Area Under the Plasma Concentration-time Profile From Time Zero to the Last Quantifiable Concentration (AUClast)
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Assessment method [16]
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At each designated time point, blood samples (3 mL) for pharmacokinetic (PK) analysis of crizotinib and its metabolite, PF 06260182 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included AUClast for crizotinib and PF-06260182. AUClast was calculated using Linear/Log trapezoidal method.
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Timepoint [16]
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Cycle 1 (C1)/Day 1 (D1), C1D15
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Secondary outcome [17]
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Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Area Under the Plasma Concentration-time Curve 10 (AUC10)
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Assessment method [17]
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At each designated time point, blood samples (3 mL) for pharmacokinetic (PK) analysis of crizotinib and its metabolite, PF 06260182 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). AUC10 was calculated using Linear/Log trapezoidal method. The below analysis table included geometric Mean and Geometric Coefficient of Variation of AUC10 for crizotinib and PF-06260182. Arithmetic mean was presented if the n=2.
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Timepoint [17]
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C1D1, C1D15
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Secondary outcome [18]
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Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Maximum Plasma Concentration (Cmax)
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Assessment method [18]
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At each designated time point, blood samples (3 mL) for pharmacokinetic (PK) analysis of crizotinib and its metabolite, PF 06260182 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included Cmax for crizotinib and PF-06260182. Cmax was observed directly from data.
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Timepoint [18]
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0
C1D1, C1D15
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Secondary outcome [19]
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Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase - Time of Last Quantifiable Concentration (Tlast)
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Assessment method [19]
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At each designated time point, blood samples (3 mL) for pharmacokinetic (PK) analysis of crizotinib and its metabolite, PF 06260182 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included Tlast for crizotinib and PF-06260182. Tlast was observed directly from data.
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Timepoint [19]
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0
C1D1, C1D15
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Secondary outcome [20]
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0
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Escalation Phase -Time to Maximum Plasma Concentration (Tmax)
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Assessment method [20]
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At each designated time point, blood samples (3 mL) for pharmacokinetic (PK) analysis of crizotinib and its metabolite, PF 06260182 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included Tmax for crizotinib and PF-06260182. Tmax was observed directly from data as time of first occurrence.
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Timepoint [20]
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0
C1D1, C1D15
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Secondary outcome [21]
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0
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - AUClast
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Assessment method [21]
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At each designated time point, blood samples (3 mL) for PK analysis of dacomitinib and its metabolite, PF 05199265 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included AUClast for dacomitinib and PF-05199265. AUClast was calculated using Linear/Log trapezoidal method.
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Timepoint [21]
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0
C1D1, C1D15
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Secondary outcome [22]
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0
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - AUC24
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Assessment method [22]
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0
At each designated time point, blood samples (3 mL) for PK analysis of dacomitinib and its metabolite, PF 05199265 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included AUC24 for dacomitinib and PF-05199265. AUC24 was calculated using Linear/Log trapezoidal method.
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Timepoint [22]
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0
C1D1, C1D15
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Secondary outcome [23]
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0
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - Cmax
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Assessment method [23]
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0
At each designated time point, blood samples (3 mL) for PK analysis of dacomitinib and its metabolite, PF 05199265 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included Cmax for dacomitinib and PF-05199265. Cmax was observed directly from data.
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Timepoint [23]
0
0
C1D1, C1D15
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Secondary outcome [24]
0
0
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - Tlast
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Assessment method [24]
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0
At each designated time point, blood samples (3 mL) for PK analysis of dacomitinib and its metabolite, PF 05199265 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included Tlast for dacomitinib and PF-05199265. Tlast was observed directly from data.
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Timepoint [24]
0
0
C1D1, C1D15
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Secondary outcome [25]
0
0
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Escalation Phase - Tmax
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Assessment method [25]
0
0
At each designated time point, blood samples (3 mL) for PK analysis of dacomitinib and its metabolite, PF 05199265 were collected in appropriately labeled collection tubes containing dipotassium ethylenediamine tetra-acetic acid (K2EDTA). The below analysis table included Tmax for dacomitinib and PF-05199265. Tmax was observed directly from data as time of first occurrence.
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Timepoint [25]
0
0
C1D1, C1D15
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Secondary outcome [26]
0
0
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - AUClast
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Assessment method [26]
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0
Participants were evaluated for the effect of dacomitinib on steady-state PK of crizotinib. PK of crizotinib alone was evaluated on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) after a lead in period of continuous BID dosing of crizotinib for approximately 12 days (±2 days). PK of crizotinib and dacomitinib in combination treatment was evaluated on Day 1 of Cycle 2. Blood samples for crizotinib full PK were to be collected on Day -1 and Day 1 of Cycle 2. The below table included PK data for AUClast. AUClast was calculated using Linear/Log trapezoidal method.
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Timepoint [26]
0
0
Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib)
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Secondary outcome [27]
0
0
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - AUC10
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Assessment method [27]
0
0
Participants were evaluated for the effect of dacomitinib on steady-state PK of crizotinib. PK of crizotinib alone was evaluated on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) after a lead in period of continuous BID dosing of crizotinib for approximately 12 days (±2 days). PK of crizotinib and dacomitinib in combination treatment was evaluated on Day 1 of Cycle 2. Blood samples for crizotinib full PK were to be collected on Day -1 and Day 1 of Cycle 2. The below table included PK data for AUC10. AUC10 was calculated using Linear/Log trapezoidal method.
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Timepoint [27]
0
0
Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib)
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Secondary outcome [28]
0
0
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - Cmin
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Assessment method [28]
0
0
Participants were evaluated for the effect of dacomitinib on steady-state PK of crizotinib. PK of crizotinib alone was evaluated on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) after a lead in period of continuous BID dosing of crizotinib for approximately 12 days (±2 days). PK of crizotinib and dacomitinib in combination treatment was evaluated on Day 1 of Cycle 2. Blood samples for crizotinib full PK were to be collected on Day -1 and Day 1 of Cycle 2. The below table included PK data for Cmin. Cmin was observed directly from data.
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Timepoint [28]
0
0
Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib)
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Secondary outcome [29]
0
0
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - Cmax
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Assessment method [29]
0
0
Participants were evaluated for the effect of dacomitinib on steady-state PK of crizotinib. PK of crizotinib alone was evaluated on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) after a lead in period of continuous BID dosing of crizotinib for approximately 12 days (±2 days). PK of crizotinib and dacomitinib in combination treatment was evaluated on Day 1 of Cycle 2. Blood samples for crizotinib full PK were to be collected on Day -1 and Day 1 of Cycle 2. The below table included PK data for Cmax. Cmax was observed directly from data.
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Timepoint [29]
0
0
Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib)
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Secondary outcome [30]
0
0
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - Tlast
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Assessment method [30]
0
0
Participants were evaluated for the effect of dacomitinib on steady-state PK of crizotinib. PK of crizotinib alone was evaluated on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) after a lead in period of continuous BID dosing of crizotinib for approximately 12 days (±2 days). PK of crizotinib and dacomitinib in combination treatment was evaluated on Day 1 of Cycle 2. Blood samples for crizotinib full PK were to be collected on Day -1 and Day 1 of Cycle 2. The below table included PK data for Tlast. Tlast was observed directly from data.
Query!
Timepoint [30]
0
0
Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib)
Query!
Secondary outcome [31]
0
0
Plasma Crizotinib and PF-06260182 Pharmacokinetic Parameter in Expansion Cohort 1 With or Without Co-administration of Dacomitinib - Tmax
Query!
Assessment method [31]
0
0
Participants were evaluated for the effect of dacomitinib on steady-state PK of crizotinib. PK of crizotinib alone was evaluated on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) after a lead in period of continuous BID dosing of crizotinib for approximately 12 days (±2 days). PK of crizotinib and dacomitinib in combination treatment was evaluated on Day 1 of Cycle 2. Blood samples for crizotinib full PK were to be collected on Day -1 and Day 1 of Cycle 2. The below table included PK data for Tmax. Tmax was observed directly from data as time of first occurrence.
Query!
Timepoint [31]
0
0
Day -1 (crizotinib alone), C2D1 (crizotinib + dacomitinib)
Query!
Secondary outcome [32]
0
0
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - AUClast
Query!
Assessment method [32]
0
0
PK samples for full PK evaluation of dacomitinib were drawn on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) and on C2D1. Dacomitinib and PF-05199265 PK parameter (AUClast) following dacomitinib alone and in combination with crizotinib are summarized in the below table. AUClast was calculated using Linear/Log trapezoidal method.
Query!
Timepoint [32]
0
0
Day -1 (dacomitinib alone), C2D1 (crizotinib + dacomitinib)
Query!
Secondary outcome [33]
0
0
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - AUC24
Query!
Assessment method [33]
0
0
PK samples for full PK evaluation of dacomitinib were drawn on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) and on C2D1. Dacomitinib and PF-05199265 PK parameter (AUC24) following dacomitinib alone and in combination with crizotinib are summarized in the below table. AUC24 was calculated using Linear/Log trapezoidal method.
Query!
Timepoint [33]
0
0
Day -1 (dacomitinib alone), C2D1 (crizotinib + dacomitinib)
Query!
Secondary outcome [34]
0
0
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - Cmin
Query!
Assessment method [34]
0
0
PK samples for full PK evaluation of dacomitinib were drawn on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) and on C2D1. Dacomitinib and PF-05199265 PK parameter (Cmin) following dacomitinib alone and in combination with crizotinib are summarized in the below table. Cmin was observed directly from data.
Query!
Timepoint [34]
0
0
Day -1 (dacomitinib alone), C2D1 (crizotinib + dacomitinib)
Query!
Secondary outcome [35]
0
0
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - Cmax
Query!
Assessment method [35]
0
0
PK samples for full PK evaluation of dacomitinib were drawn on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) and on C2D1. Dacomitinib and PF-05199265 PK parameter (Cmax) following dacomitinib alone and in combination with crizotinib are summarized in the below table. Cmax was observed directly from data.
Query!
Timepoint [35]
0
0
Day -1 (dacomitinib alone), C2D1 (crizotinib + dacomitinib)
Query!
Secondary outcome [36]
0
0
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - Tlast
Query!
Assessment method [36]
0
0
PK samples for full PK evaluation of dacomitinib were drawn on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) and on C2D1. Dacomitinib and PF-05199265 PK parameter (Tlast) following dacomitinib alone and in combination with crizotinib are summarized in the below table. Tlast was observed directly from data.
Query!
Timepoint [36]
0
0
Day -1 (dacomitinib alone), C2D1 (crizotinib + dacomitinib)
Query!
Secondary outcome [37]
0
0
Plasma Dacomitinib and PF-05199265 Pharmacokinetic Parameter in Expansion Cohort 2 With or Without Co-administration of Dacomitinib - Tmax
Query!
Assessment method [37]
0
0
PK samples for full PK evaluation of dacomitinib were drawn on Day -1 (one day before C1D1 on which the combination treatment of crizotinib and dacomitinib started) and on C2D1. Dacomitinib and PF-05199265 PK parameter (Tmax) following dacomitinib alone and in combination with crizotinib are summarized in the below table. Tmax was observed directly from data as time of first occurrence.
Query!
Timepoint [37]
0
0
Day -1 (dacomitinib alone), C2D1 (crizotinib + dacomitinib)
Query!
Eligibility
Key inclusion criteria
* advanced non small cell lung cancer (dose escalation phase)
* acquired resistance to erlotinib or gefitinib (expansion phase)
* mandatory entrance biopsy (expansion phase)
Query!
Minimum age
18
Years
Query!
Query!
Maximum age
No limit
Query!
Query!
Sex
Both males and females
Query!
Can healthy volunteers participate?
No
Query!
Key exclusion criteria
* interstitial lung disease
* unstable brain metastases
* leptomeningeal disease
Query!
Study design
Purpose of the study
Treatment
Query!
Allocation to intervention
Non-randomised trial
Query!
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Query!
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Query!
Masking / blinding
Open (masking not used)
Query!
Who is / are masked / blinded?
Query!
Query!
Query!
Query!
Intervention assignment
Parallel
Query!
Other design features
Query!
Phase
Phase 1
Query!
Type of endpoint/s
Query!
Statistical methods / analysis
Query!
Recruitment
Recruitment status
Completed
Query!
Data analysis
Query!
Reason for early stopping/withdrawal
Query!
Other reasons
Query!
Date of first participant enrolment
Anticipated
Query!
Actual
1/08/2010
Query!
Date of last participant enrolment
Anticipated
Query!
Actual
Query!
Date of last data collection
Anticipated
Query!
Actual
1/02/2014
Query!
Sample size
Target
Query!
Accrual to date
Query!
Final
70
Query!
Recruitment in Australia
Recruitment state(s)
VIC
Query!
Recruitment hospital [1]
0
0
Peter MacCallum Cancer Centre, Division of Haematology and Medical Oncology - East Melbourne
Query!
Recruitment postcode(s) [1]
0
0
3002 - East Melbourne
Query!
Recruitment outside Australia
Country [1]
0
0
United States of America
Query!
State/province [1]
0
0
Colorado
Query!
Country [2]
0
0
United States of America
Query!
State/province [2]
0
0
Maryland
Query!
Country [3]
0
0
United States of America
Query!
State/province [3]
0
0
Massachusetts
Query!
Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Query!
Name
Pfizer
Query!
Address
Query!
Country
Query!
Ethics approval
Ethics application status
Query!
Summary
Brief summary
Lung cancer tumors become resistant to the first generation epidermal growth factor receptor (EGFR) inhibitors erlotinib or gefitinib by changing and increasing the activity of two cell signaling pathways: the cMET pathway and the EGFR pathway. Both resistance mechanisms can occur at the same time, in the same patient and even in the same tumor. This study combines a second generation EGFR inhibitor and a cMET inhibitor to block both these pathways in order to overcome resistance and treat this disease.
Query!
Trial website
https://clinicaltrials.gov/study/NCT01121575
Query!
Trial related presentations / publications
Query!
Public notes
Query!
Contacts
Principal investigator
Name
0
0
Pfizer CT.gov Call Center
Query!
Address
0
0
Pfizer
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for public queries
Name
0
0
Query!
Address
0
0
Query!
Country
0
0
Query!
Phone
0
0
Query!
Fax
0
0
Query!
Email
0
0
Query!
Contact person for scientific queries
No information has been provided regarding IPD availability
What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results are available at
https://clinicaltrials.gov/study/NCT01121575
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